Viral Delivery of CAR Targets to Solid Tumors Enables Effective Cell Therapy

Molecular Therapy: Oncolytics

Alexander X. Lozano¹  Surya Murty¹  Fabrice Le Boeuf²  John C. Bell²  Matthew Tang³  Federico Simonetta³  Travis M. Shaffer⁴  Amin Aalipour⁴  Sanjiv S. Gambhir⁵ 

[1] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada;Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA 94305, USA;Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada;Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA;Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA;

关键词: chimeric antigen receptor;    oncolytic virus;    CAR T cells;    vaccinia virus;    solid tumor;    immunotherapy;   

DOI  :  

来源: DOAJ

【 摘 要 】

Chimeric antigen receptor (CAR) T cell therapy has had limited efficacy for solid tumors, largely due to a lack of selectively and highly expressed surface antigens. To avoid reliance on a tumor’s endogenous antigens, here we describe a method of tumor-selective delivery of surface antigens using an oncolytic virus to enable a generalizable CAR T cell therapy. Using CD19 as our proof of concept, we engineered a thymidine kinase-disrupted vaccinia virus to selectively deliver CD19 to malignant cells, and thus demonstrated potentiation of CD19 CAR T cell activity against two tumor types in vitro. In an immunocompetent model of B16 melanoma, this combination markedly delayed tumor growth and improved median survival compared with antigen-mismatched combinations. We also found that CD19 delivery could improve CAR T cell activity against tumor cells that express low levels of cognate antigen, suggesting a potential application in counteracting antigen-low escape. This approach highlights the potential of engineering tumors for effective adoptive cell therapy.

【 授权许可】

Unknown